The long term goal of this research project is to develop new single photon emission computed tomography (SPECT) system designs for improved imaging and characterization of Tc-99m radiopharmaceutical uptake in early-stage breast cancer. The concepts being considered have multiple tiltable cameras, equipped with convergent beam or pinhole collimators, revolving around a single breast, with the patient in a prone position, aligned with the camera's vertical axis of rotation (VAOR). The main hypothesis is that a multiple-camera VAOR SPECT system with convergent beam collimators can improve lesion detectability over planar scintimammography, as well as over conventional SPECT (i.e., horizontal axis of rotation devices requiring a large radius of rotation). Also, it is hypothesized that VAOR SPECT, when used in conjunction with image reconstruction algorithms which compensate for attenuation, detected Compton scatter events and collimator resolution, is capable of detecting small breast cancers less than 8 mm in diameter and with a tumor-to-background activity concentration ratio less than 6 to 1. Compared with conventional SPECT systems, the primary advantages of the proposed design are: i) minimal radius of rotation by including one breast alone in the field-of-view, ii) improved system sensitivity and resolution due to the use of multiple cameras and convergent beam or pinhole collimators specially designed for breast imaging, iii) reduced attenuation for the photons emitted from the breast, iv) less overlying and underlying torso activities in the camera's field-of-view if existing myocardial imaging pharmaceuticals are used, and v) tiltable cameras provide a flexibility to extend the imaged region to include near-chest-wall tissue with little camera-patient interference. We propose to investigate these hypotheses by evaluating alternative system configurations, deriving reconstruction algorithms for preferred system configurations, evaluating lesion detectability by conducting receiver operating characteristics studies, and comparing VAOR SPECT with planar scintimammography and conventional horizontal axis of rotation SPECT. The specific aims of this proposal are: i) designing VAOR acquisition system configurations for breast cancer imaging, ii) developing new image reconstruction algorithms for selected configurations, and iii) evaluating selected configurations and image reconstruction algorithms. Although building a VAOR SPECT system is beyond the scope of this initial proposal, clinical applicability will be demonstrated using a horizontal axis of rotation SPECT device with tiltable detectors to serve as a test facility for initial VAOR feasibility scans.